Oncogenic mutations in Ras-encoding genes are found in approximately 30% of all tumors and are most prevalent in carcinomas of the pancreas, colon, lung and bladder. These mutations have profound effects on proliferation, cell survival and tumor invasion. Ras orchestrates these events by activating downstream effector pathways that regulate actin reorganization, gene expression and macropinocytosis.
Macropinocytosis is a stimulated form of fluid-phase uptake that involves extensive plasma membrane remodeling and the internalization of extracellular fluid via large endocytic structures called macropinosomes. Macropinocytosis plays a key role in various biological processes, including immune surveillance, nutrient uptake and pathogen infection. Interestingly, macropinocytosis is also stimulated in cells harboring oncogenic mutations; however, the functional significance of this stimulation is unknown.
The present invention is directed to overcoming these and other deficiencies in the art.